This proposal is in response to the human genome initiative to map and sequence the human genome. The regions chosen are the area on the distal short arm of the X chromosome proximal to the pseudoautosomal junction, and the proximal long arm of the Y chromosome. These two regions of the sex chromosomes share extensive sequence homology. Several genes and genetic diseases have been mapped to these regions and a significant fraction of these chromosome segments have already been cloned. Contig maps of these two regions will be constructed and gene sequences will be located. Sequence-tagged sites at an average spacing of 100 kb will be established, To speed up the cloning process strategies have been designed which make use of the homology shared between these two regions and the availability of patients with interstitial deletions within these regions. Human libraries using both cosmids and yeast artificial chromosomes as cloning vectors will be used. The maps constructed will enhance our understanding of the structure and sequence organization of the human genome and the ordered clones will be available for future large scale sequencing studies. The cloned ends of the contig maps will provide new starting points for future cloning and mapping of the adjacent areas.